Inverted microscope configurations and computer control for automatic focusing and microscope stage positioning have been used for imaging of biological samples, for example, U.S. Pat. No. 4,000,417 discloses a computer automated system for blood cell counts and blood cell morphology studies. The system provides automated x-y stage translation, auto-focusing, and an automated meander search pattern system for cell finding. The system also provides for memorization of x-y positions for re-insertion of slides and re-viewing of previously viewed cells on previously used slides. U.S. Pat. No. 6,005,964 discloses an automatic microscope slide inspection system with a controllable stage positioner for scanning slides for pathogenic protozoa. U.S. Pat. Nos. 4,705,949 and 4,974,952 disclose cell chambers or holders microscopy of living cell specimens. U.S. Pat. No. 4,920,053 discloses a method for micromanipulation of living cells using an inverted microscope, and U.S. Pat. No. 5,991,028 discloses an automated spectral imaging system for cell classification. Ultramicroscopy 2001, April; 87(3): 155–64 discloses a method of two-photon 4Pi confocal fluorescence microscopy for imaging of live cells. Environmental Health Perspective 1999, November; 107(11) discloses a technique for imaging of living cells using an integrated optical magnetic resonance microscope. Folia Histochem Cytobiol 2001;39(2):75–85 discloses the use of confocal microscopy for fluorescently labeled thick specimens of stained living cells without requiring physical sectioning of samples.
Additional patents of interest include U.S. Pat. Nos. 4,920,053, 5,991,028, 4,705,949, 5,594,235, 6,005,964, 5,861,985, 4,000,417, 6,049,421, 6,246,785 and 4,958,920, the disclosures of which are incorporated herein by reference. Publications of interest include Anal Biochem Jun. 15, 2001;293(2):258–63, Ultramicroscopy 2001, April;87(3): 155–64, Folia Histochem Cytobiol 2001;39(2):75–85, Trends Cell Biol 2001 August;11(8): 329–34, J Microbiol Methods 2000 October;42(2):129–38, J Immunol Methods Nov. 19, 1999;230(1–2): 11–8, and Environmental Health Perspective 1999, November; 107(11); and Nature 2001 May; 411: 107–110. the disclosures of which are incorporated herein by reference.
Still, no available microscopy systems effectively provide for high throughput techniques for observation of living cells, with imaging of living cells carried out in a multi-well format. Particularly, no microscopy systems allow rapid imaging of living cells in a multi-well format without harm to the living cells, or allow quick and easy re-imaging of previously viewed living cells. The present invention satisfies these needs, as well as others, and overcomes deficiencies found in the background references.